Laboratory of Proteins Engineering and Bioactive Molecules (LIP-MB), INSAT, University of Tunis Carthage, Tunis, Tunisia.
UOSD SAFU, Department of Research, Diagnosis and Innovative Technologies, IRCCS-Regina Elena National Cancer Institute, Rome, Italy.
J Clin Lab Anal. 2022 Sep;36(9):e24606. doi: 10.1002/jcla.24606. Epub 2022 Jul 19.
Several studies have interrogated the molecular pathways and their interacting genes underlying bladder cancer (BCa) tumorigenesis, yet, the role of homeobox genes is still poorly understood. Specifically, HOXA13, which plays an important role as a major actor in the urogenital tract's development.
Immunohistochemical (IHC) staining was performed to inspect the differential expression of HOXA13 protein in non-muscle-invasive bladder cancer (NMIBC) and non-tumoral tissues. A semiquantitative scoring system was adopted to evaluate the IHC labeling. Correlation to clinical parameters was performed by descriptive statistics. Overall survival was estimated by the Kaplan-Meier method and Cox regression model. The functional HOX A13 protein association networks (PPI) were obtained using String 11.0 database.
HOX A13 exhibited cytoplasmic and nuclear staining. Its expression levels were lower in high-grade NMIBC (HG NMIBC) compared to low-grade ones (LG NMIBC). The expression of HOX A13 was correlated to tumor grade (LG/HG) (p = 0.036) and stage (TA/T1) (p = 0.036). Nevertheless, its expression was not correlated to clinical parameters and was not able to predict the overall survival of patients with HG NMIBC. Finally, PPI analysis revealed that HOX A13 seems to be a part of a molecular network holding mainly PBX1, MEIS, ALDH1A2, HOX A10, and HOX A11.
The deregulation of HOX A13 is not associated with the prognosis of BCa. It seems to be rather implicated in the early initiation of urothelial tumorigenesis and thus may serve as a diagnostic marker in patients with NMIBC. Further experimentations on larger validation sets are mandatory.
已有多项研究探讨了膀胱癌（BCa）肿瘤发生的分子途径及其相互作用的基因，但同源盒基因的作用仍知之甚少。具体而言，HOXA13 在尿生殖系统发育中作为主要因子发挥重要作用。
采用免疫组织化学（IHC）染色法检测非肌层浸润性膀胱癌（NMIBC）和非肿瘤组织中 HOXA13 蛋白的差异表达。采用半定量评分系统评估 IHC 标记。采用描述性统计学方法对临床参数进行相关性分析。采用 Kaplan-Meier 法和 Cox 回归模型估计总生存期。使用 String 11.0 数据库获得具有功能的 HOXA13 蛋白关联网络（PPI）。
HOXA13 表现为细胞质和核染色。高级别 NMIBC（HG NMIBC）中 HOXA13 的表达水平低于低级别 NMIBC（LG NMIBC）。HOXA13 的表达与肿瘤分级（LG/HG）（p=0.036）和分期（TA/T1）（p=0.036）相关。然而，其表达与临床参数无关，不能预测 HG NMIBC 患者的总生存期。最后，PPI 分析表明，HOXA13 似乎是一个分子网络的一部分，该网络主要包含 PBX1、MEIS、ALDH1A2、HOXA10 和 HOXA11。
HOXA13 的失调与 BCa 的预后无关。它似乎更多地参与了尿路上皮肿瘤的早期发生，因此可能作为 NMIBC 患者的诊断标志物。需要对更大的验证集进行进一步的实验。
